Current Genetics

, Volume 65, Issue 5, pp 1121–1125 | Cite as

(p)ppGpp: the magic governor of bacterial growth economy

  • Manlu ZhuEmail author
  • Yige Pan
  • Xiongfeng DaiEmail author


A fundamental question in microbiology is how bacterial cells manage to coordinate gene expression with cell growth during adapting to various environmental conditions. Although the cellular responses to changing environments have been extensively studied using transcriptomic and proteomic approaches, it remains poorly understood regarding the molecular strategy enabling bacteria to manipulate the global gene expression patterns. The alarmone (p)ppGpp is a key secondary messenger involved in regulating various biochemical and physiological processes of bacterial cells. However, despite of the extensive studies of (p)ppGpp signaling in stringent response during the past 50 years, the connection between (p)ppGpp and exponential growth remains poorly understood. Our recent work demonstrates that (p)ppGpp is strongly involved in regulating cell growth of Escherichia coli through balancing the cellular investment on metabolic proteins and ribosomes, highlighting itself as a magic governor of bacterial global resource allocation. In this mini-review, we briefly summarize some historical perspectives and current progress of the relation between (p)ppGpp and bacterial exponential growth. Two important future directions are also highlighted: the first direction is to elucidate the cellular signal that triggers (p)ppGpp accumulation during poor growth conditions; the second direction is to investigate the relation between (p)ppGpp and exponential growth for bacterial species other than E. coli.


(p)ppGpp Exponential growth Resource allocation 



This work was supported by the National Natural Science Fund of China (nos. 31700089, 31700039 and 31870028) and by self-determined research funds of CCNU from the colleges’ basic research and operation of MOE.


  1. Bremer H, Dennis P (1996) Modulation of chemical composition and other parameters of the cell at different exponential growth rates. Escherichia coli and Salmonella, ed Neidhardt FC (Am Soc Microbiol, Washington, DC) 2:1553–1569Google Scholar
  2. Castro-Cerritos KV, Lopez-Torres A, Obregón-Herrera A, Wrobel K, Wrobel K, Pedraza-Reyes M (2018) LC–MS/MS proteomic analysis of starved Bacillus subtilis cells overexpressing ribonucleotide reductase (nrdEF): implications in stress-associated mutagenesis. Curr Genet 64(1):215–222CrossRefGoogle Scholar
  3. Cook GM, Berney M, Gebhard S, Heinemann M, Cox RA, Danilchanka O, Niederweis M (2009) Physiology of mycobacteria. Adv Microb Physiol 55:81–182CrossRefGoogle Scholar
  4. Dai X, Zhu M, Warren M, Balakrishnan R, Patsalo V, Okano H, Williamson JR, Fredrick K, Wang YP, Hwa T (2016) Reduction of translating ribosomes enables Escherichia coli to maintain elongation rates during slow growth. Nat Microbiol 2:16231CrossRefGoogle Scholar
  5. Dai X, Zhu M, Warren M, Balakrishnan R, Okano H, Williamson JR, Fredrick K, Hwa T (2018) Slowdown of translational elongation in Escherichia coli under hyperosmotic stress. MBio 9:1CrossRefGoogle Scholar
  6. Dalebroux ZD, Swanson MS (2012) ppGpp: magic beyond RNA polymerase. Nat Rev Microbiol 10(3):203–212CrossRefGoogle Scholar
  7. Gaal T, Gourse RL (1990) Guanosine 3′-diphosphate 5′-diphosphate is not required for growth rate-dependent control of rRNA synthesis in Escherichia coli. Proc Natl Acad Sci USA 87(14):5533–5537CrossRefGoogle Scholar
  8. Gohara DW, Yap MNF (2018) Survival of the drowsiest: the hibernating 100S ribosome in bacterial stress management. Curr Genet 64(4):753–760CrossRefGoogle Scholar
  9. Gourse RL, Chen AY, Gopalkrishnan S, Sanchez-Vazquez P, Myers A, Ross W (2018) Transcriptional Responses to ppGpp and DksA. Annu Rev Microbiol 72:163–184CrossRefGoogle Scholar
  10. Hauryliuk V, Atkinson GC, Murakami KS, Tenson T, Gerdes K (2015) Recent functional insights into the role of (p)ppGpp in bacterial physiology. Nat Rev Microbiol 13(5):298–309CrossRefGoogle Scholar
  11. Hernandez VJ, Bremer H (1990) Guanosine tetraphosphate (ppGpp) dependence of the growth rate control of rrnB P1 promoter activity in Escherichia coli. J Biol Chem 265(20):11605–11614Google Scholar
  12. Hernandez VJ, Bremer H (1993) Characterization of RNA and DNA synthesis in Escherichia coli strains devoid of ppGpp. J Biol Chem 268(15):10851–10862Google Scholar
  13. Hui S, Silverman JM, Chen SS, Erickson DW, Basan M, Wang J, Hwa T, Williamson JR (2015) Quantitative proteomic analysis reveals a simple strategy of global resource allocation in bacteria. Mol Syst Biol 11(1):784CrossRefGoogle Scholar
  14. Klumpp S, Hwa T (2014) Bacterial growth: global effects on gene expression, growth feedback and proteome partition. Curr Opin Biotechnol 28:96–102CrossRefGoogle Scholar
  15. Klumpp S, Zhang Z, Hwa T (2009) Growth rate-dependent global effects on gene expression in bacteria. Cell 139(7):1366–1375CrossRefGoogle Scholar
  16. Klumpp S, Scott M, Pedersen S, Hwa T (2013) Molecular crowding limits translation and cell growth. Proc Natl Acad Sci USA 110(42):16754–16759CrossRefGoogle Scholar
  17. Krasny L, Gourse RL (2004) An alternative strategy for bacterial ribosome synthesis: Bacillus subtilis rRNA transcription regulation. EMBO J 23(22):4473–4483CrossRefGoogle Scholar
  18. Magnusson LU, Farewell A, Nystrom T (2005) ppGpp: a global regulator in Escherichia coli. Trends Microbiol 13(5):236–242CrossRefGoogle Scholar
  19. Monod J (1949) The growth of bacterial cultures. Annu Rev Microbiol 3(1):371–394CrossRefGoogle Scholar
  20. Murphy H, Cashel M (2003) Isolation of RNA polymerase suppressors of a (p)ppGpp deficiency. Methods Enzymol 371:596–601CrossRefGoogle Scholar
  21. Murray DK, Bremer H (1996) Control of spoT-dependent ppGpp synthesis and degradation in Escherichia coli. J Mol Biol 259(1):41–57CrossRefGoogle Scholar
  22. Paul BJ, Ross W, Gaal T, Gourse RL (2004) rRNA transcription in Escherichia coli. Annu Rev Genet 38:749–770CrossRefGoogle Scholar
  23. Potrykus K, Cashel M (2008) (p)ppGpp: still magical? Annu Rev Microbiol 62:35–51CrossRefGoogle Scholar
  24. Potrykus K, Murphy H, Philippe N, Cashel M (2011) ppGpp is the major source of growth rate control in E. coli. Environ Microbiol 13(3):563–575CrossRefGoogle Scholar
  25. Scott M, Hwa T (2011) Bacterial growth laws and their applications. Curr Opin Biotechnol 22(4):559–565CrossRefGoogle Scholar
  26. Scott M, Gunderson CW, Mateescu EM, Zhang Z, Hwa T (2010) Interdependence of cell growth and gene expression: origins and consequences. Science 330(6007):1099–1102CrossRefGoogle Scholar
  27. Scott M, Klumpp S, Mateescu EM, Hwa T (2014) Emergence of robust growth laws from optimal regulation of ribosome synthesis. Mol Syst Biol 10:747CrossRefGoogle Scholar
  28. Srivatsan A, Wang JD (2008) Control of bacterial transcription, translation and replication by (p)ppGpp. Curr Opin Microbiol 11(2):100–105CrossRefGoogle Scholar
  29. Steinchen W, Bange G (2016) The magic dance of the alarmones (p)ppGpp. Mol Microbiol 101(4):531–544CrossRefGoogle Scholar
  30. Sun D, Lee G, Lee JH, Kim HY, Rhee HW, Park SY, Kim KJ, Kim Y, Kim BY, Hong JI, Park C, Choy HE, Kim JH, Jeon YH, Chung J (2010) A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses. Nat Struct Mol Biol 17(10):1188–1194CrossRefGoogle Scholar
  31. Xiao H, Kalman M, Ikehara K, Zemel S, Glaser G, Cashel M (1991) Residual guanosine 3′,5′-bispyrophosphate synthetic activity of relA null mutants can be eliminated by spoT null mutations. J Biol Chem 266(9):5980–5990Google Scholar
  32. You C, Okano H, Hui S, Zhang Z, Kim M, Gunderson CW, Wang YP, Lenz P, Yan D, Hwa T (2013) Coordination of bacterial proteome with metabolism by cyclic AMP signalling. Nature 500(7462):301–306CrossRefGoogle Scholar
  33. Zhu M, Dai X (2019) Growth suppression by altered (p)ppGpp levels results from non-optimal resource allocation in Escherichia coli. Nucleic Acids Res gkz211.

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Life SciencesCentral China Normal UniversityWuhanChina

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